112423 20240319080951.0 doi 10.1038/s41598-022-07281-6 sideral 128373 ART-2022-128373 eng Belkahla, Sana The metabolism of cells regulates their sensitivity to NK cells depending on p53 status 2022 Access copy available to the general public Unrestricted Leukemic cells proliferate faster than non-transformed counterparts. This requires them to change their metabolism to adapt to their high growth. This change can stress cells and facilitate recognition by immune cells such as cytotoxic lymphocytes, which express the activating receptor Natural Killer G2-D (NKG2D). The tumor suppressor gene p53 regulates cell metabolism, but its role in the expression of metabolism-induced ligands, and subsequent recognition by cytotoxic lymphocytes, is unknown. We show here that dichloroacetate (DCA), which induces oxidative phosphorylation (OXPHOS) in tumor cells, induces the expression of such ligands, e.g. MICA/B, ULBP1 and ICAM-I, by a wtp53-dependent mechanism. Mutant or null p53 have the opposite effect. Conversely, DCA sensitizes only wtp53-expressing cells to cytotoxic lymphocytes, i.e. cytotoxic T lymphocytes and NK cells. In xenograft in vivo models, DCA slows down the growth of tumors with low proliferation. Treatment with DCA, monoclonal antibodies and NK cells also decreased tumors with high proliferation. Treatment of patients with DCA, or a biosimilar drug, could be a clinical option to increase the effectiveness of CAR T cell or allogeneic NK cell therapies. info:eu-repo/grantAgreement/ES/DGA/B31-20R info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.6 2022 MULTIDISCIPLINARY SCIENCES 22 / 73 = 0.301 2022 Q2 T1 0.973 2022 Multidisciplinary 2022 Q1 7.5 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Brualla, Joaquín Marco Universidad de Zaragoza Fayd'herbe de Maudave, Alexis Falvo, Paolo Allende-Vega, Nerea Constantinides, Michael Khan, Abrar Ul Haq Coenon, Lois Alexia, Catherine Mitola, Giulia Massa, Paul Orecchioni, Stefania Bertolini, Francesco Mnif, Wissem Hernandez, Javier Anel, Alberto Universidad de Zaragoza (orcid)0000-0002-5175-8394 Villalba, Martin 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 12 (2022), 3234 [13 pp.] Sci. rep. (Nat. Publ. Group) Scientific reports (Nature Publishing Group) 2045-2322 1309923 http://zaguan.unizar.es/record/112423/files/texto_completo.pdf Versión publicada 2693335 http://zaguan.unizar.es/record/112423/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:112423 articulos driver 2024-03-18-13:02:52 ARTICLE